A Study of Adalimumab in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis

Ulcerative Colitis Clinical Trial

Official title:

A Multi-Center, Randomized, Double-Blind, Placebo-controlled Study of Adalimumab in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00853099
• Other study ID #: M10-447
• Status: Completed
• Phase: Phase 3
• First received: February 27, 2009
• Last updated: September 3, 2014
• Start date: February 2009
• Est. completion date: August 2013

Study information

• Verified date: September 2014
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the efficacy and safety of adalimumab in Japanese subjects with moderately to severely active ulcerative colitis (UC).

Description:

Patients who meet all of the inclusion criteria and none of the exclusion criteria are randomized 1:1:1 to receive subcutaneous injections of adalimumab at either 160/80 mg at Week 0/2 and 40 mg every other week (eow) starting at Week 4 to Week 50, 80/40 mg at Week 0/2 and 40 mg eow starting at Week 4 to Week 50, or placebo eow starting at Week 0 to Week 50 under the double-blind condition. At or after Week 8, participants who have inadequate response during the double-blind period can switch to the rescue arm, where participants from the placebo group initially receive adalimumab 160 mg and 80 mg 2 weeks later and those from the adalimumab group receive adalimumab 40 mg initially and 2 weeks later under double-blind conditions. All participants in the rescue arm then receive 40 mg adalimumab eow until Week 50. Participants who complete the 52-week double-blind period receive open-label adalimumab 40 mg eow starting at Week 52 and continuing until the end of the study. Participants who have an inadequate response or disease flare can dose escalate to 80 mg eow at or after Week 60. Participants who dose escalate to 80 mg eow and continue to have an inadequate response or disease flare are withdrawn from the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 274
• Est. completion date: August 2013
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of ulcerative colitis for greater than 90 days prior to Baseline.

• Active ulcerative colitis with a Mayo Score of 6-12 points at Baseline and endoscopy subscore of 2-3 during the Screening Period, despite concurrent treatment with at least one of the following (oral corticosteroids or immunosuppressants or both as defined below):

• Stable oral corticosteroid dose (prednisolone dose of = 20 mg/day or equivalent) for at least 14 days prior to Baseline or stable oral corticosteroid dose (prednisolone of 5 to less than 20 mg/day) for at least 40 days prior to Baseline. And/or

• At least a consecutive 90-day course of azathioprine or 6-mercaptopurine (6-MP) prior to Baseline, with a dose of azathioprine = 50 mg/day or 6-MP = 30 mg/day, or a dose that was the highest tolerated by the patient.

Exclusion Criteria:

• History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, or ileostomy for ulcerative colitis or was planning bowel surgery.

• Patients with disease limited to the rectum.

• Indeterminate colitis and/or Crohn's disease.

• Received any biological therapy (including infliximab) in the past.

• History of tuberculosis or malignancy.

• Pregnant women.

• Patients with positive C. difficile stool assay at Screening.

• Current diagnosis of fulminant colitis and/or toxic megacolon.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Biological:
• adalimumab

Drug:
• placebo

Locations

Country	Name	City	State
Japan	Site Reference ID/Investigator# 47136	Asahikawa
Japan	Site Reference ID/Investigator# 47159	Chiba
Japan	Site Reference ID/Investigator# 47183	Chikushino
Japan	Site Reference ID/Investigator# 47135	Fukuoka-shi
Japan	Site Reference ID/Investigator# 47182	Fukuoka-shi
Japan	Site Reference ID/Investigator# 47124	Hamamatsu
Japan	Site Reference ID/Investigator# 47130	Hirakata-shi
Japan	Site Reference ID/Investigator# 47103	Hirosaki
Japan	Site Reference ID/Investigator# 47178	Hiroshima
Japan	Site Reference ID/Investigator# 47179	Hiroshima
Japan	Site Reference ID/Investigator# 47131	Hiroshima-shi
Japan	Site Reference ID/Investigator# 47176	Izumo
Japan	Site Reference ID/Investigator# 47226	Kagoshima
Japan	Site Reference ID/Investigator# 47123	Kanazawa-shi
Japan	Site Reference ID/Investigator# 47160	Kashiwa
Japan	Site Reference ID/Investigator# 47108	Kawagoe
Japan	Site Reference ID/Investigator# 47107	Koshigaya
Japan	Site Reference ID/Investigator# 47181	Kurume
Japan	Site Reference ID/Investigator# 47222	Kurume
Japan	Site Reference ID/Investigator# 47223	Kurume
Japan	Site Reference ID/Investigator# 47127	Kyoto
Japan	Site Reference ID/Investigator# 47172	Kyoto
Japan	Site Reference ID/Investigator# 47170	Kyoto-shi
Japan	Site Reference ID/Investigator# 47171	Kyoto-shi
Japan	Site Reference ID/Investigator# 47134	Matsuyama-shi
Japan	Site Reference ID/Investigator# 47225	Miyazaki
Japan	Site Reference ID/Investigator# 47138	Morioka-shi
Japan	Site Reference ID/Investigator# 47168	Nagakute-shi
Japan	Site Reference ID/Investigator# 47125	Nagoya-shi
Japan	Site Reference ID/Investigator# 47126	Nagoya-shi
Japan	Site Reference ID/Investigator# 47166	Nagoya-shi
Japan	Site Reference ID/Investigator# 47122	Niigata-shi
Japan	Site Reference ID/Investigator# 47227	Nishihara
Japan	Site Reference ID/Investigator# 47174	Nishinomiya-shi
Japan	Site Reference ID/Investigator# 47224	Oita
Japan	Site Reference ID/Investigator# 47177	Okayama-shi
Japan	Site Reference ID/Investigator# 47228	Okinawa
Japan	Site Reference ID/Investigator# 47129	Osaka
Japan	Site Reference ID/Investigator# 47128	Osaka-shi
Japan	Site Reference ID/Investigator# 47169	Otsu-shi
Japan	Site Reference ID/Investigator# 47118	Sagamihara-shi
Japan	Site Reference ID/Investigator# 47158	Saitama-shi
Japan	Site Reference ID/Investigator# 47109	Sakura
Japan	Site Reference ID/Investigator# 47137	Sapporo
Japan	Site Reference ID/Investigator# 15853	Sapporo-shi
Japan	Site Reference ID/Investigator# 47104	Sendai-shi
Japan	Site Reference ID/Investigator# 47147	Sendai-shi
Japan	Site Reference ID/Investigator# 47180	Susaki-shi
Japan	Site Reference ID/Investigator# 47133	Takamatsu
Japan	Site Reference ID/Investigator# 47173	Takatsuki-shi
Japan	Site Reference ID/Investigator# 47106	Tokorozawa-shi
Japan	Site Reference ID/Investigator# 47132	Tokushima
Japan	Site Reference ID/Investigator# 47110	Tokyo
Japan	Site Reference ID/Investigator# 47111	Tokyo
Japan	Site Reference ID/Investigator# 47112	Tokyo
Japan	Site Reference ID/Investigator# 47116	Tokyo
Japan	Site Reference ID/Investigator# 47117	Tokyo
Japan	Site Reference ID/Investigator# 47161	Tokyo
Japan	Site Reference ID/Investigator# 47164	Tokyo
Japan	Site Reference ID/Investigator# 47165	Toyama
Japan	Site Reference ID/Investigator# 47167	Toyoake
Japan	Site Reference ID/Investigator# 47105	Yamagata-shi
Japan	Site Reference ID/Investigator# 47175	Yamatotakada
Japan	Site Reference ID/Investigator# 47120	Yokohama
Japan	Site Reference ID/Investigator# 47121	Yokohama-shi

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie (prior sponsor, Abbott)	Eisai Co., Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Clinical Remission at 8 Weeks	Clinical remission was defined as a Mayo score = 2 with no individual subscore > 1. The Mayo score is a composite score of ulcerative colitis disease activity calculated as the sum of four subscores: Stool Frequency Subscore (SFS), based on the participant's diary and scored from zero (normal number of stools) to three (5 or more stools than normal); Rectal Bleeding Subscore (RBS), based on the participant's diary and scored from zero (no blood) to three (blood only passed); Endoscopy Subscore (ESS), based on colonoscopy or sigmoidoscopy and scored from zero (normal or inactive disease) to three (severe disease, spontaneous bleeding, ulceration); Physician's Global Assessment (PGA) subscore, based on the physician's overall assessment, and scored from zero (normal) to three (severe disease).; The total Mayo score ranges from 0 to 12 points, with higher scores representing more severe disease.	Week 8	No
Primary	Percentage of Participants With Clinical Remission at 52 Weeks	Clinical remission was defined as a Mayo score = 2 with no individual subscore > 1. The Mayo score is a composite score of ulcerative colitis disease activity calculated as the sum of four subscores: Stool Frequency Subscore (SFS), based on the participant's diary and scored from zero (normal number of stools) to three (5 or more stools than normal); Rectal Bleeding Subscore (RBS), based on the participant's diary and scored from zero (no blood) to three (blood only passed); Endoscopy Subscore (ESS), based on colonoscopy or sigmoidoscopy and scored from zero (normal or inactive disease) to three (severe disease, spontaneous bleeding, ulceration); Physician's Global Assessment (PGA) subscore, based on the physician's overall assessment, and scored from zero (normal) to three (severe disease).; The total Mayo score ranges from 0 to 12 points, with higher scores representing more severe disease.	Week 52	No
Secondary	Percentage of Participants With Clinical Remission at 8, 32, and 52 Weeks	Clinical remission was defined as a Mayo score = 2 with no individual subscore > 1. The Mayo score is a composite score of ulcerative colitis disease activity calculated as the sum of four subscores: Stool Frequency Subscore (SFS), based on the participant's diary and scored from zero (normal number of stools) to three (5 or more stools than normal); Rectal Bleeding Subscore (RBS), based on the participant's diary and scored from zero (no blood) to three (blood only passed); Endoscopy Subscore (ESS), based on colonoscopy or sigmoidoscopy and scores from zero (normal or inactive disease) to three (severe disease, spontaneous bleeding, ulceration); Physician's Global Assessment (PGA) subscore, based on the physician's overall assessment, and scored from zero (normal) to three (severe disease).; The total Mayo score ranges from 0 to 12 points, with higher scores representing more severe disease.	Weeks 8, 32, and 52	No
Secondary	Percentage of Participants With a Clinical Response	A clinical response was defined as a decrease in Mayo score of = 3 points and = 30% from Baseline PLUS a decrease in the Rectal Bleeding Subscore (RBS) = 1 or an absolute RBS of 0 or 1.; The Mayo score is a composite score of ulcerative colitis disease activity calculated as the sum of four subscores: Stool Frequency Subscore, based on the participant's diary and scored from zero (normal number of stools) to three (5 or more stools than normal); Rectal Bleeding Subscore, based on the participant's diary and scored from zero (no blood) to three (blood only passed); Endoscopy Subscore, based on colonoscopy or sigmoidoscopy and scored from zero (normal or inactive disease) to three (severe disease, spontaneous bleeding, ulceration); Physician's Global Assessment subscore, based on the physician's overall assessment, and scored from zero (normal) to three (severe disease).; The total Mayo score ranges from 0 to 12 points, with higher scores representing more severe disease.	Baseline and Weeks 8, 32, and 52	No
Secondary	Percentage of Participants With Mucosal Healing	Mucosal healing was defined as an endoscopy subscore of = 1 and was assessed using flexible sigmoidoscopy performed at Weeks 8, 32, and 52.; The endoscopy subscore ranges from zero to three as follows: 0 = Normal or inactive disease, 1 = Mild disease (erythema, decreased vascular pattern, mild friability), 2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions), 3 = Severe disease (spontaneous bleeding, ulceration).	Weeks 8, 32, and 52	No
Secondary	Percentage of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (= 1)	Rectal bleeding was assessed from the participant's diary, taking the worst score from the 3 days prior to each study visit. The rectal bleeding subscore ranges from zero to three, according to the following scale: 0 = no blood seen, 1 = streaks of blood with stool less than half the time, 2 = obvious blood with stool most of the time, 3 = blood alone passed.	Weeks 8, 32, and 52	No
Secondary	Percentage of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (= 1)	The Physician's Global Assessment Subscore acknowledges the three other subscores (Stool Frequency, Rectal Bleeding, and Endoscopy), the participant's daily record of abdominal discomfort and functional assessment, and other observations such as physical findings and the participant's performance status. Possible scores range from zero to three as follows: 0 = Normal (other subscores are 0), 1 = Mild disease (other subscores are mostly 1), 2 = Moderate disease (other subscores are 1 to 2), 3 = Severe disease (other subscores are 2 to 3).	Weeks 8, 32, and 52	No
Secondary	Percentage of Participants With Stool Frequency Subscore Indicative of Mild Disease (= 1)	Stool frequency was assessed from the participant's diary, taking the worst score from the 3 days prior to each study visit. The stool frequency subscore ranges from zero to three, according to the following scale: 0 = Normal number of stools for this participant, 1 = 1-2 stools more than normal, 2 = 3-4 stools more than normal, 3 = 5 or more stools more than normal.	Weeks 8, 32, and 52	No
Secondary	Percentage of Inflammatory Bowel Disease Questionnaire (IBDQ) Responders	An inflammatory bowel disease questionnaire responder was defined as a participant with at least a 16-point increase from Baseline in total Inflammatory Bowel Disease Questionnaire (IBDQ) score. The IBDQ is a 32-item questionnaire consisting of 4 dimensions: bowel-related symptoms, systemic function, social function, and emotional status. The responses to each question within each domain range from 1 (significant impairment) to 7 (no impairment), with the total score ranging from 32 (very poor) to 224 (perfect health-related quality of life).	Baseline and Weeks 8, 32, and 52	No
Secondary	Number of Participants With Adverse Events up to Week 8	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.; The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related.; A serious adverse event is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.; For more details on adverse events please see the Adverse Event section below.	8 weeks	Yes
Secondary	Number of Participants With Adverse Events up to Week 52	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.; The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related.; A serious adverse event is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.; For more details on adverse events please see the Adverse Event section below.	52 weeks	Yes
Secondary	Number of Participants With Adverse Events During the Adalimumab Treatment Period	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.; The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related.; A serious adverse event is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.; For more details on adverse events please see the Adverse Event section below.	221 weeks	Yes

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